Letter to the Editor
Hereditary optic neuropathy and associated systemic diseases due to 2 overlapping mitochondrial mutations
Neuropatía óptica hereditaria y síndromes sistémicos asociados como resultado del solapamiento de 2 mutaciones mitocondriales
C. Gutiérrez-Ortiz, S. Rodrigo-Rey
Corresponding author
Departamento de oftalmología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain
Read
1418
Timeswas read the article
251
Total PDF
1167
Total HTML
Share statistics
array:25 [ "pii" => "S2173580821000523" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.07.020" "estado" => "S300" "fechaPublicacion" => "2021-07-01" "aid" => "1490" "copyright" => "Sociedad Española de Neurología" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:472-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S0213485320302541" "issn" => "02134853" "doi" => "10.1016/j.nrl.2020.07.021" "estado" => "S300" "fechaPublicacion" => "2021-07-01" "aid" => "1490" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:472-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Neuropatía óptica hereditaria y síndromes sistémicos asociados como resultado del solapamiento de 2 mutaciones mitocondriales" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "472" "paginaFinal" => "473" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Hereditary optic neuropathy and systemic disease of the overlapping of two mitochondrial mutations" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 775 "Ancho" => 1668 "Tamanyo" => 64748 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Funduscopia de ambos ojos, observándose palidez de predominio temporal.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Gutiérrez-Ortiz, S. Rodrigo-Rey" "autores" => array:2 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Gutiérrez-Ortiz" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Rodrigo-Rey" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173580821000523" "doi" => "10.1016/j.nrleng.2020.07.020" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821000523?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485320302541?idApp=UINPBA00004N" "url" => "/02134853/0000003600000006/v1_202106290536/S0213485320302541/v1_202106290536/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2173580821000511" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.06.012" "estado" => "S300" "fechaPublicacion" => "2021-07-01" "aid" => "1489" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:474-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Experience of using subcutaneous levetiracetam in palliative patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "474" "paginaFinal" => "475" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Experiencia de uso de levetiracetam subcutáneo en pacientes paliativos" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Más-Sesé, D. Martín-Bautista, A. Navarro-Catalá" "autores" => array:3 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Más-Sesé" ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Martín-Bautista" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Navarro-Catalá" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S021348532030253X" "doi" => "10.1016/j.nrl.2020.06.017" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S021348532030253X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821000511?idApp=UINPBA00004N" "url" => "/21735808/0000003600000006/v1_202107061645/S2173580821000511/v1_202107061645/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S217358082100050X" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.04.023" "estado" => "S300" "fechaPublicacion" => "2021-07-01" "aid" => "1469" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "pgl" "cita" => "Neurologia. 2021;36:462-71" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Consensus statement</span>" "titulo" => "Stroke prevention in patients with arterial hypertension: Recommendations of the Spanish Society of Neurology's Stroke Study Group" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "462" "paginaFinal" => "471" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prevención de ictus en pacientes con hipertensión arterial: recomendaciones del Grupo de Estudio de Enfermedades Cerebrovasculares de la Sociedad Española de Neurología" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Rodríguez-Yañez, M. Gómez-Choco, E. López-Cancio, S. Amaro, M. Alonso de Leciñana, J.F. Arenillas, O. Ayo-Martín, M. Castellanos, M.M. Freijo, A. García-Pastor, M. Gomis, P. Martínez Sánchez, A. Morales, E.J. Palacio-Portilla, J. Roquer, T. Segura, J. Serena, J. Vivancos-Mora, B. Fuentes" "autores" => array:20 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Rodríguez-Yañez" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Gómez-Choco" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "López-Cancio" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Amaro" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Alonso de Leciñana" ] 5 => array:2 [ "nombre" => "J.F." "apellidos" => "Arenillas" ] 6 => array:2 [ "nombre" => "O." "apellidos" => "Ayo-Martín" ] 7 => array:2 [ "nombre" => "M." "apellidos" => "Castellanos" ] 8 => array:2 [ "nombre" => "M.M." "apellidos" => "Freijo" ] 9 => array:2 [ "nombre" => "A." "apellidos" => "García-Pastor" ] 10 => array:2 [ "nombre" => "M." "apellidos" => "Gomis" ] 11 => array:2 [ "nombre" => "P." "apellidos" => "Martínez Sánchez" ] 12 => array:2 [ "nombre" => "A." "apellidos" => "Morales" ] 13 => array:2 [ "nombre" => "E.J." "apellidos" => "Palacio-Portilla" ] 14 => array:2 [ "nombre" => "J." "apellidos" => "Roquer" ] 15 => array:2 [ "nombre" => "T." "apellidos" => "Segura" ] 16 => array:2 [ "nombre" => "J." "apellidos" => "Serena" ] 17 => array:2 [ "nombre" => "J." "apellidos" => "Vivancos-Mora" ] 18 => array:2 [ "nombre" => "B." "apellidos" => "Fuentes" ] 19 => array:1 [ "colaborador" => "ad hoc committee of the Spanish Society of Neurology's Study Group for Cerebrovascular Diseases" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485320302292" "doi" => "10.1016/j.nrl.2020.04.031" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485320302292?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217358082100050X?idApp=UINPBA00004N" "url" => "/21735808/0000003600000006/v1_202107061645/S217358082100050X/v1_202107061645/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Hereditary optic neuropathy and associated systemic diseases due to 2 overlapping mitochondrial mutations" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "472" "paginaFinal" => "473" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "C. Gutiérrez-Ortiz, S. Rodrigo-Rey" "autores" => array:2 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Gutiérrez-Ortiz" ] 1 => array:4 [ "nombre" => "S." "apellidos" => "Rodrigo-Rey" "email" => array:1 [ 0 => "sara.rodrigor@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de oftalmología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neuropatía óptica hereditaria y síndromes sistémicos asociados como resultado del solapamiento de 2 mutaciones mitocondriales" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 775 "Ancho" => 1667 "Tamanyo" => 63190 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fundus examination of both eyes, revealing predominantly temporal pallor.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We present the ophthalmological examination of a patient diagnosed with myoclonic epilepsy with ragged red fibres (MERRF) syndrome associated with Madelung disease (multiple symmetric lipomatosis), who was a carrier of the T14484C primary mitochondrial mutation, related to Leber hereditary optic neuropathy (LHON).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Madelung disease is a rare condition (1:25 000) characterised by multiple non-encapsulated lipomas symmetrically distributed around the neck and shoulder girdle.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It may be associated with other neuropathies, myopathies, or autonomous nervous system involvement.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Its aetiology is unknown,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> but most cases are associated with alcohol abuse,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> liver transplantation,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> and endocrine or metabolic diseases (diabetes mellitus, hyperuricaemia, and hypercholesterolaemia).<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The m8344A>G mitochondrial DNA mutation associated with MERRF syndrome is present in 10% of the cases.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Clinical case</span><p id="par0015" class="elsevierStylePara elsevierViewall">We present the case of a 63-year-old woman with no toxic habits who presented neck lipomas secondary to Madelung disease; Wolf–Parkinson–White (WPW) syndrome; and polyneuropathies and myoclonus; her symptoms were already described in an article by López-Blanco et al.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Her mother presented tremor and lipomas, with the latter also manifesting in the patient’s sister.</p><p id="par0020" class="elsevierStylePara elsevierViewall">She reported progressive, painless impairment of visual acuity (VA) in the right eye (OD), progressing for one year (VA OD: 0.7; VA OS: 1). We observed bitemporal pallor of both optic nerves (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Visual field examination revealed concentric defects in both eyes (OU) and decreased general sensitivity, with no defect in central vision (visual field index and mean defect of 80% and –11.20 dB in OD and 75% and –11.21 dB in OS). The patient was able to distinguish 2 of the 12 plates of the Ishihara test. Optical coherence tomography revealed decreased thickness of the retinal nerve fibre layer, predominantly affecting the temporal region (mean of 60 μm in OU), and a generalised loss of ganglion cells (mean of 52 m in OD and 54 m in OS) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Results of the multifocal electroretinography (ERG) were normal, and the N95 wave was altered in the pattern ERG.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Brain magnetic resonance imaging revealed supra- and infratentorial atrophy without thickening of the optic nerves in T2-weighted sequences. Electromyography and electrocardiogram results supported the diagnosis of polyneuropathy and WPW syndrome.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Genetic testing showed 2 mitochondrial DNA mutations: m8344A>G and T14484C. A muscle biopsy confirmed presence of ragged red fibres.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Therefore, the patient was diagnosed with MERRF syndrome in addition to Madelung disease, and was a carrier of one of the primary mutations associated with LHON.</p><p id="par0045" class="elsevierStylePara elsevierViewall">We recommended that drugs toxic to the respiratory chain be avoided and that treatment be started with coenzyme Q10.</p><p id="par0050" class="elsevierStylePara elsevierViewall">During follow-up (2 years), visual acuity has been stable.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0055" class="elsevierStylePara elsevierViewall">Our patient shows a peculiar overlap of 2 mitochondrial mutations, which affect several organs with high energy demand<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> (heart, skeletal muscles, brain, and visual system, particularly the papillomacular bundle).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Mutations causing MERRF affect mitochondrial respiratory chain function and protein synthesis. Typical features include myoclonus, myelopathy, and spasticity, together with peripheral neuropathies. Patients frequently present short stature and rarely present lipomas. They may also present ataxia, deafness, dementia, and in some cases, epilepsy. Some cases also show optic atrophy and retinopathy.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Bearing in mind that our patient presents 2 mutations potentially responsible for the visual impairment (m8344A>G and T14484C), which each provoke ophthalmological symptoms in 20% of cases, we consider the m8344A>G mutation the main cause of the impairment, and not the mutation associated with LHON, for several reasons: epidemiology (the patient was a woman) and pathochronia (unilateral, progressive vision loss) are not typical of LHON; and the relatively preserved central vision and the visual field defect without central involvement are also not suggestive of LHON.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The pattern ERG showed an alteration of the N95 wave with normal P50 wave, which suggests altered ganglion cells.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Optic disc microangiopathy (pseudoedema, hyperaemia, peripapillary telangiectasias, and oedema of the retinal nerve fibre layer) and late-onset optic atrophy are characteristic of LHON; furthermore, the optic nerve may be thickened in T2-weighted magnetic resonance sequences. Our patient’s WPW syndrome may be related to the T14484C mutation.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Very few cases or families presenting Madelung disease in association with the m8344A>G mutation and MERRF syndrome have been identified, and to our knowledge, no overlap with the T14484C mutation related to LHON<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> has been reported; this case shows the best prognosis. In this case, it was not possible to perform genetic testing of family members, as they were not covered by our healthcare district.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In conclusion, we described the ophthalmological manifestations secondary to this overlap of mitochondrial mutations.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Clinical case" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-03-17" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Gutiérrez-Ortiz C, Rodrigo-Rey S. Neuropatía óptica hereditaria y síndromes sistémicos asociados como resultado del solapamiento de 2 mutaciones mitocondriales. Neurología. 2021;36:472–473.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 775 "Ancho" => 1667 "Tamanyo" => 63190 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Fundus examination of both eyes, revealing predominantly temporal pallor.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1373 "Ancho" => 1667 "Tamanyo" => 251959 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Complementary tests, including optical coherence tomography and visual field.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beyond cervical lipomas: myoclonus, gait disorder and multisystem involvement leading to mitochondrial disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. López-Blanco" 1 => "A. Rojo-Sebastián" 2 => "M. Torregrosa-Martínez" 3 => "A. Blazquez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bcr-2016-218861" "Revista" => array:2 [ "tituloSerie" => "BMJ Case Rep." "fecha" => "2017" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple symmetric lipomatosis: case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Meningaud" 1 => "P. Pitak-Arnnop" 2 => "J. Bertrand" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.joms.2005.10.045" "Revista" => array:6 [ "tituloSerie" => "J Oral Maxillofac Surg." "fecha" => "2007" "volumen" => "65" "paginaInicial" => "1365" "paginaFinal" => "1369" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17577504" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple symmetric lipomatosis: a diagnostic dilemma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Mimica" 1 => "D. Pravdic" 2 => "E. Nakas-Icindic" 3 => "M. Karin" 4 => "E. Babic" 5 => "M. Tomic" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2013/836903" "Revista" => array:2 [ "tituloSerie" => "Case Rep Med." "fecha" => "2013" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondrial dysfunction in multiple symmetrical lipomatosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Berkovic" 1 => "F. Andermann" 2 => "E. Shoubridge" 3 => "S. Carpenter" 4 => "Y. Robitaille" 5 => "E. Andermann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ana.410290519" "Revista" => array:6 [ "tituloSerie" => "Ann Neurol." "fecha" => "1991" "volumen" => "29" "paginaInicial" => "566" "paginaFinal" => "569" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1650162" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Symmetric benign lipomatosis; Madelung syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Ballester Sánchez" 1 => "M. Navarro Mira" 2 => "C. Pujol Marco" 3 => "R. Botella Estrada" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medcli.2013.01.031" "Revista" => array:6 [ "tituloSerie" => "Med Clin (Barc)." "fecha" => "2013" "volumen" => "141" "paginaInicial" => "366" "paginaFinal" => "367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23540382" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Madelung’s disease—progressive, excessive, and symmetrical deposition of adipose tissue in the subcutaneous layer: case report and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Szewc" 1 => "R. Sitarz" 2 => "N. Moroz" 3 => "R. Maciejewski" 4 => "R. Wierzbicki" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Diabetes Metab Syndr Obes." "fecha" => "2018" "volumen" => "26" "paginaInicial" => "819" "paginaFinal" => "825" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hereditary Madelung’s disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C. Payne" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/014107680009300411" "Revista" => array:6 [ "tituloSerie" => "J R Soc Med." "fecha" => "2000" "volumen" => "93" "paginaInicial" => "194" "paginaFinal" => "195" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10844887" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial multiple symmetric lipomatosis associated with the A8344G mutation of mitochondria DNA" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Gámez" 1 => "A. Playán" 2 => "A.L. Andreu" 3 => "C. Bruno" 4 => "C. Navarro" 5 => "C. Cervera" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1212/wnl.51.1.258" "Revista" => array:6 [ "tituloSerie" => "Neurology." "fecha" => "1998" "volumen" => "51" "paginaInicial" => "258" "paginaFinal" => "260" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9674814" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondrial optic neuropathies—disease mechanisms and therapeutic strategies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Yu-Wai-Man" 1 => "P. Griffiths" 2 => "P. Chinnery" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.preteyeres.2010.11.002" "Revista" => array:6 [ "tituloSerie" => "Prog Retin Eye Res." "fecha" => "2011" "volumen" => "30" "paginaInicial" => "81" "paginaFinal" => "114" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21112411" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A review of mitochondrial optic neuropathies: from inherited to acquired forms" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Y. Pliz" 1 => "S. Bass" 2 => "J. Sherman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.optom.2016.09.003" "Revista" => array:6 [ "tituloSerie" => "J Optom." "fecha" => "2017" "volumen" => "10" "paginaInicial" => "205" "paginaFinal" => "214" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28040497" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "MERRF classification: implications for diagnosis and clinical trials" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Finsterer" 1 => "S. Zarrouk-Mahjoub" 2 => "J. Shoffner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pediatrneurol.2017.12.005" "Revista" => array:6 [ "tituloSerie" => "Pediatr Neurol." "fecha" => "2018" "volumen" => "80" "paginaInicial" => "8" "paginaFinal" => "23" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29449072" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phenotypic heterogeneity of the 8344A>G mtDNA «MERRF» mutation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Mancuso" 1 => "D. Orsucci" 2 => "C. Angelini" 3 => "E. Bertini" 4 => "V. Carelli" 5 => "G.P. Comi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1212/WNL.0b013e318294b44c" "Revista" => array:6 [ "tituloSerie" => "Neurology." "fecha" => "2013" "volumen" => "80" "paginaInicial" => "2049" "paginaFinal" => "2054" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23635963" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hereditary optic neuropathies: from the mitochondria to the optic nerve" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N. Newman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajo.2005.03.017" "Revista" => array:6 [ "tituloSerie" => "Am J Ophthalmol." "fecha" => "2005" "volumen" => "140" "paginaInicial" => "517" "paginaFinal" => "523" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16083845" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ISCEV guide to visual electrodiagnostic procedures" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.G. Robson" 1 => "J. Nilsson" 2 => "S. Li" 3 => "S. Jalali" 4 => "A.B. Fulton" 5 => "A.P. Tormene" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10633-018-9634-1" "Revista" => array:6 [ "tituloSerie" => "Doc Ophthalmol." "fecha" => "2018" "volumen" => "136" "paginaInicial" => "1" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29785579" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High incidence of pre-excitation syndrome in Japanese families with Leber’s hereditary optic neuropathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y. Mashima" 1 => "K. Kigasawa" 2 => "H. Hasegawa" 3 => "M. Tani" 4 => "Y. Oguchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-0004.1996.tb02732.x" "Revista" => array:6 [ "tituloSerie" => "Clin Genet." "fecha" => "1996" "volumen" => "50" "paginaInicial" => "535" "paginaFinal" => "537" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9147893" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735808/0000003600000006/v1_202107061645/S2173580821000523/v1_202107061645/en/main.assets" "Apartado" => array:4 [ "identificador" => "9409" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735808/0000003600000006/v1_202107061645/S2173580821000523/v1_202107061645/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821000523?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 3 | 0 | 3 |
| 2024 October | 24 | 3 | 27 |
| 2024 September | 25 | 3 | 28 |
| 2024 August | 32 | 3 | 35 |
| 2024 July | 20 | 4 | 24 |
| 2024 June | 28 | 1 | 29 |
| 2024 May | 20 | 4 | 24 |
| 2024 April | 25 | 4 | 29 |
| 2024 March | 39 | 8 | 47 |
| 2024 February | 41 | 2 | 43 |
| 2024 January | 32 | 11 | 43 |
| 2023 December | 33 | 5 | 38 |
| 2023 November | 30 | 4 | 34 |
| 2023 October | 22 | 9 | 31 |
| 2023 September | 16 | 7 | 23 |
| 2023 August | 16 | 5 | 21 |
| 2023 July | 16 | 5 | 21 |
| 2023 June | 22 | 2 | 24 |
| 2023 May | 59 | 5 | 64 |
| 2023 April | 45 | 1 | 46 |
| 2023 March | 26 | 2 | 28 |
| 2023 February | 39 | 4 | 43 |
| 2023 January | 31 | 4 | 35 |
| 2022 December | 46 | 6 | 52 |
| 2022 November | 41 | 4 | 45 |
| 2022 October | 40 | 6 | 46 |
| 2022 September | 21 | 10 | 31 |
| 2022 August | 46 | 6 | 52 |
| 2022 July | 32 | 8 | 40 |
| 2022 June | 90 | 7 | 97 |
| 2022 May | 22 | 5 | 27 |
| 2022 April | 30 | 10 | 40 |
| 2022 March | 13 | 10 | 23 |
| 2022 February | 23 | 5 | 28 |
| 2022 January | 34 | 6 | 40 |
| 2021 December | 13 | 10 | 23 |
| 2021 November | 12 | 7 | 19 |
| 2021 October | 18 | 15 | 33 |
| 2021 September | 9 | 14 | 23 |
| 2021 August | 20 | 9 | 29 |
| 2021 July | 13 | 9 | 22 |
| 2021 June | 0 | 5 | 5 |
| 2021 May | 0 | 3 | 3 |
| 2021 April | 0 | 0 | 0 |
Show all
